Physiological Mechanisms of Airway Hyperresponsiveness in Obese Asthma.

Abstract:

:Obesity affects the incidence and severity of asthma in at least two major phenotypes: an early-onset allergic (EOA) form that is complicated by obesity and a late-onset nonallergic (LONA) form that occurs only in the setting of obesity. Both groups exhibit airway hyperresponsiveness to methacholine challenge but exhibit differential effects of weight loss. Measurements of lung function in patients with LONA obese asthma suggest that this group of individuals may simply be those unlucky enough to have airways that are more compliant than average, and that this leads to airway hyperresponsiveness at the reduced lung volumes caused by excess adipose tissue around the chest wall. In contrast, the frequent exacerbations in those with EOA obese asthma can potentially be explained by episodic inflammatory thickening of the airway wall synergizing with obesity-induced reductions in lung volume. These testable hypotheses are based on the strong likelihood that LONA and EOA obese asthma are distinct diseases. Both, however, may benefit from targeted therapeutics that impose elevations in lung volume.

authors

Bates JH

doi

10.1165/rcmb.2016-0019PS

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

618-23

issue

5

eissn

1044-1549

issn

1535-4989

journal_volume

54

pub_type

杂志文章,评审
  • Modulators of sphingolipid metabolism reduce lung inflammation.

    abstract::The investigation of novel targets for the treatment of cystic fibrosis (CF) lung inflammation is a major priority, considering that no effective therapy is available for this purpose. Consistent with the evidence that the sphingolipid (SL) ceramide regulates airway inflammation and infection in mice and patients with...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2010-0457OC

    authors: Dechecchi MC,Nicolis E,Mazzi P,Cioffi F,Bezzerri V,Lampronti I,Huang S,Wiszniewski L,Gambari R,Scupoli MT,Berton G,Cabrini G

    更新日期:2011-10-01 00:00:00

  • Th1/Th2 cytokines reciprocally regulate in vitro pulmonary angiogenesis via CXC chemokine synthesis.

    abstract::Hypervascularity is known as an important element of airway remodeling in bronchial asthma. However, it remains obscure how allergic inflammation relates to angiogenesis in the lung. In this study, we examined the in vitro effects of inflammatory cytokines on endothelial cell functions, particularly angiogenesis. Huma...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0162OC

    authors: Matsuda A,Fukuda S,Matsumoto K,Saito H

    更新日期:2008-02-01 00:00:00

  • Evidence for Scgb1a1(+) cells in the generation of p63(+) cells in the damaged lung parenchyma.

    abstract::Transformation-related protein 63-expressing (p63(+)) basal cells are confined to the trachea in the mouse lung. However, after influenza virus infection or bleomycin treatment, patches of p63(+) cells were observed in the damaged lung parenchyma. To address whether the newly induced p63(+) cells are derived from the ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0327OC

    authors: Zheng D,Yin L,Chen J

    更新日期:2014-03-01 00:00:00

  • Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice.

    abstract::Identification of the genetic loci underlying asthma in humans has been hampered by variability in clinical phenotype, uncontrolled environmental influences, and genetic heterogeneity. To circumvent these complications, the genetic regulation of asthma-associated phenotypes was studied in a murine model. We characteri...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.23.4.4199

    authors: Ewart SL,Kuperman D,Schadt E,Tankersley C,Grupe A,Shubitowski DM,Peltz G,Wills-Karp M

    更新日期:2000-10-01 00:00:00

  • Interleukin-1 family member 9 stimulates chemokine production and neutrophil influx in mouse lungs.

    abstract::Interleukin-1 (IL-1) is a proinflammatory cytokine that signals through the Type I IL-1 receptor (IL-1RI). Novel IL-1-like cytokines were recently identified. Their functions in lung disease remain unclear. Interleukin-1 family member-9 (IL-1F9) is one such IL-1-like cytokine, expressed in the lungs of humans and mice...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2009-0315OC

    authors: Ramadas RA,Ewart SL,Medoff BD,LeVine AM

    更新日期:2011-02-01 00:00:00

  • Evidence against a role of mouse, rat, and two cloned human t1alpha isoforms as a water channel or a regulator of aquaporin-type water channels.

    abstract::T1alpha is a protein of unknown function that is expressed at the plasma membrane in epithelia involved in fluid transport, including type I alveolar epithelial cells, choroid plexus, and ciliary epithelium. The purpose of this study was to test the hypothesis that T1alpha functions as a water channel or a regulator o...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.19.1.2953

    authors: Ma T,Yang B,Matthay MA,Verkman AS

    更新日期:1998-07-01 00:00:00

  • Post-infection A77-1726 blocks pathophysiologic sequelae of respiratory syncytial virus infection.

    abstract::Despite respiratory syncytial virus (RSV) bronchiolitis remaining the most common cause of lower respiratory tract disease in infants worldwide, treatment has progressed little in the past 30 years. The aim of our study was to determine whether post-infection administration of de novo pyrimidine synthesis inhibitors c...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0142OC

    authors: Davis IC,Lazarowski ER,Chen FP,Hickman-Davis JM,Sullender WM,Matalon S

    更新日期:2007-10-01 00:00:00

  • Immunohistochemical detection of intracellular tropoelastin: an assay for elastin production and its use in the detection and assessment of elastogenic factors.

    abstract::Techniques are described for visualizing intracellular tropoelastin at the light level using immunofluorescence and immunogold techniques. Best results were obtained with B5 fixative on cells permeabilized with acetone. Using either formaldehyde or paraformaldehyde for fixation (instead of B5) resulted in both less re...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/3.1.45

    authors: Grosso LE,Whitehouse LA,Mecham RP

    更新日期:1990-07-01 00:00:00

  • Maintenance of airway epithelium in acutely rejected orthotopic vascularized mouse lung transplants.

    abstract::Lung transplantation remains the only therapeutic option for many patients suffering from end-stage pulmonary disease. Long-term success after lung transplantation is severely limited by the development of bronchiolitis obliterans. The murine heterotopic tracheal transplantation model has been widely used for studies ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0257RC

    authors: Okazaki M,Gelman AE,Tietjens JR,Ibricevic A,Kornfeld CG,Huang HJ,Richardson SB,Lai J,Garbow JR,Patterson GA,Krupnick AS,Brody SL,Kreisel D

    更新日期:2007-12-01 00:00:00

  • TOLL-interacting Protein in Pulmonary Diseases: Abiding by the Goldilocks Principle.

    abstract::Toll-interacting protein (TOLLIP) is an intracellular adaptor protein with diverse actions throughout the body. In a context- and cell type-specific manner, TOLLIP can function as an inhibitor of inflammation and endoplasmic reticulum stress, an activator of autophagy, or a critical regulator of intracellular vacuole ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2020-0470TR

    authors: Li X,Goobie GC,Gregory AD,Kass DJ,Zhang Y

    更新日期:2020-11-24 00:00:00

  • Inhibition of Macrophage Complement Receptor CRIg by TRIM72 Polarizes Innate Immunity of the Lung.

    abstract::The complement system plays a critical role in immune responses against pathogens. However, its identity and regulation in the lung are not fully understood. This study aimed to explore the role of tripartite motif protein (TRIM) 72 in regulating complement receptor (CR) of the Ig superfamily (CRIg) in alveolar macrop...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2017-0236OC

    authors: Nagre N,Cong X,Terrazas C,Pepper I,Schreiber JM,Fu H,Sill JM,Christman JW,Satoskar AR,Zhao X

    更新日期:2018-06-01 00:00:00

  • Evidence for stem-cell niches in the tracheal epithelium.

    abstract::It is generally important to elucidate airway epithelial cell lineages and to identify multipotent progenitors as targets for gene therapy. Stem (S) cells are typically present in specialized compartments spatially proximal to their differentiated progeny, but an equivalent paradigm has not been demonstrated in the ai...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.24.6.4217

    authors: Borthwick DW,Shahbazian M,Krantz QT,Dorin JR,Randell SH

    更新日期:2001-06-01 00:00:00

  • Molecular responses to hyperoxia in vivo: relationship to increased tolerance in aged rats.

    abstract::In this study, we have used the rat model of hyperoxia to examine the molecular responses to oxidative stress in lung. We show that in addition to the antioxidant enzyme manganese superoxide dismutase, expression of a variety of stress-responsive genes including heme oxygenase-1, c-fos, c-jun, CAAT-enhancer binding pr...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.13.1.7598940

    authors: Choi AM,Sylvester S,Otterbein L,Holbrook NJ

    更新日期:1995-07-01 00:00:00

  • Competition between elastase and related proteases from human neutrophil for binding to alpha1-protease inhibitor.

    abstract::The protease-antiprotease imbalance that is characteristic of most inflammatory lung disorders depends on the spatial-temporal regulation of active inhibitor and protease concentrations in lung secretions. We have studied the competition between the three main serine proteases from human neutrophil primary granules in...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2004-0374OC

    authors: Korkmaz B,Poutrain P,Hazouard E,de Monte M,Attucci S,Gauthier FL

    更新日期:2005-06-01 00:00:00

  • TNF-alpha sensitizes normal and fibrotic human lung fibroblasts to Fas-induced apoptosis.

    abstract::Pulmonary accumulation of fibroblasts and myofibroblasts in idiopathic pulmonary fibrosis/usual interstitial pneumonia (IFP/UIP) has been linked to (1) increased migration of a circulating pool of fibrocytes, (2) cell proliferation, and (3) resistance to apoptosis. The mechanism of physiologic apoptosis of lung fibrob...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2005-0155OC

    authors: Frankel SK,Cosgrove GP,Cha SI,Cool CD,Wynes MW,Edelman BL,Brown KK,Riches DW

    更新日期:2006-03-01 00:00:00

  • Pseudomonas aeruginosa induction of apoptosis in respiratory epithelial cells: analysis of the effects of cystic fibrosis transmembrane conductance regulator dysfunction and bacterial virulence factors.

    abstract::Airway epithelial cells can respond to infection by activating several signaling pathways. We examined the induction of apoptosis in response to Pseudomonas aeruginosa PAO1 in normal cells and several cystic fibrosis (CF) and corrected cell lines. Epithelial cells in monolayers with tight junctions, confirmed by apica...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.23.3.4098

    authors: Rajan S,Cacalano G,Bryan R,Ratner AJ,Sontich CU,van Heerckeren A,Davis P,Prince A

    更新日期:2000-09-01 00:00:00

  • Prostaglandin E2 stimulates the production of vascular endothelial growth factor through the E-prostanoid-2 receptor in cultured human lung fibroblasts.

    abstract::Fibroblasts are the major mesenchymal cells present within the interstitium of the lung and are a major source of vascular endothelial growth factor (VEGF), which modulates the maintenance of pulmonary microvasculature. Prostaglandin E(2) (PGE(2)) acts on a set of E-prostanoid (EP) receptors that activate multiple sig...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2010-0115OC

    authors: Nakanishi M,Sato T,Li Y,Nelson AJ,Farid M,Michalski J,Kanaji N,Wang X,Basma H,Patil A,Goraya J,Liu X,Togo S,L Toews M,Holz O,Muller KC,Magnussen H,Rennard SI

    更新日期:2012-02-01 00:00:00

  • Endothelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis.

    abstract::The pathological hallmark lesions in idiopathic pulmonary fibrosis are the fibroblastic foci, in which fibroblasts are thought to be involved in the tissue remodeling, matrix deposition, and cross-talk with alveolar epithelium. Recent evidence indicates that some fibroblasts in fibrosis may be derived from bone marrow...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2009-0031OC

    authors: Hashimoto N,Phan SH,Imaizumi K,Matsuo M,Nakashima H,Kawabe T,Shimokata K,Hasegawa Y

    更新日期:2010-08-01 00:00:00

  • Diversity of Interstitial Lung Fibroblasts Is Regulated by Platelet-Derived Growth Factor Receptor α Kinase Activity.

    abstract::Epithelial-mesenchymal cell interactions and factors that control normal lung development are key players in lung injury, repair, and fibrosis. A number of studies have investigated the roles and sources of epithelial progenitors during lung regeneration; such information, however, is limited in lung fibroblasts. Thus...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2015-0095OC

    authors: Green J,Endale M,Auer H,Perl AK

    更新日期:2016-04-01 00:00:00

  • Early regulatory changes in rat pulmonary artery of renin-dependent systemic hypertension models.

    abstract::Patients with systemic hypertension of various etiologies maintain their pulmonary artery pressures within normal limits. We have reported in isolated perfused rat lungs that low basal tone appears to be regulated by nitric oxide (NO)-dependent and -independent mechanisms of soluble guanylate cyclase activation, and s...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.15.4.8879180

    authors: Itani MM,Talerico MG,Pino PA,Burke-Wolin T

    更新日期:1996-10-01 00:00:00

  • Histochemical and immunohistochemical characteristics of mast cells in nasal polyps.

    abstract::In surgically excised nasal polyps, most epithelial mast cells were formalin sensitive, chloroacetate esterase (CAE) negative, and chymase negative. Thus, this represents a population of mast cells not identified by staining for CAE. On the other hand, most stromal mast cells were formalin resistant and CAE positive, ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/6.1.37

    authors: Kawabori S,Denburg JA,Schwartz LB,Irani AA,Wong D,Jordana G,Evans S,Dolovich J

    更新日期:1992-01-01 00:00:00

  • Mucin biosynthesis: epidermal growth factor downregulates core 2 enzymes in a human airway adenocarcinoma cell line.

    abstract::Enzymes which exhibit core 2 beta1,6 N-acetylglucosaminyltransferase (C2GnT) activity play important roles in physiologic processes including the inflammatory response and immune system function, and C2GnT activity is regulated during processes, such as T cell activation and cellular differentiation. In this study, we...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2002-0147OC

    authors: Beum PV,Bastola DR,Cheng PW

    更新日期:2003-07-01 00:00:00

  • Pneumocystis carinii uses a functional cdc13 B-type cyclin complex during its life cycle.

    abstract::Pneumocystis carinii causes severe pneumonia in immunocompromised patients. Recent studies indicate that P. carinii uses a Cdc2 cyclin-dependent kinase to control its proliferation. To further study the regulation of the life cycle of P. carinii, we characterized the P. carinii B-type cyclin termed Cdc13, whose bindin...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.22.6.3838

    authors: Kottom TJ,Thomas CF Jr,Mubarak KK,Leof EB,Limper AH

    更新日期:2000-06-01 00:00:00

  • Expression of MUC1 mucin gene by hamster tracheal surface epithelial cells in primary culture.

    abstract::Primary hamster tracheal surface epithelial (HTSE) cells carry mucin-like glycoproteins on the apical surface which are releasable by neutrophil elastase. In some cancer cells, mucins are localized on the cell surface and have been shown to be encoded by the MUC1 mucin gene. The objectives of the present experiments w...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.15.2.8703480

    authors: Park H,Hyun SW,Kim KC

    更新日期:1996-08-01 00:00:00

  • Epithelial sodium channel inhibition in primary human bronchial epithelia by transfected siRNA.

    abstract::Na(+) absorption and Cl(-) secretion are in equilibrium to maintain an appropriate airway surface fluid volume and ensure appropriate mucociliary clearance. In cystic fibrosis, this equilibrium is disrupted by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in the absence of ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0456OC

    authors: Caci E,Melani R,Pedemonte N,Yueksekdag G,Ravazzolo R,Rosenecker J,Galietta LJ,Zegarra-Moran O

    更新日期:2009-02-01 00:00:00

  • Temporal-spatial analysis of the immune response in a murine model of ovalbumin-induced airways inflammation.

    abstract::The objective of this study was to define phenotypic changes of antigen-presenting cells (APCs) and T cells in a murine model of antigen-induced airways inflammation that involves intraperitoneal sensitization with ovalbumin (OVA)/adjuvant followed by antigen aerosolization. We investigated the APC and T-cell compartm...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.25.3.4482

    authors: Gajewska BU,Swirski FK,Alvarez D,Ritz SA,Goncharova S,Cundall M,Snider DP,Coyle AJ,Gutierrez-Ramos JC,Stämpfli MR,Jordana M

    更新日期:2001-09-01 00:00:00

  • Human ciliated bronchial epithelial cells: expression of the HLA-DR antigens and of the HLA-DR alpha gene, modulation of the HLA-DR antigens by gamma-interferon and antigen-presenting function in the mixed leukocyte reaction.

    abstract::HLA-DR class II molecules are expressed by a variety of nonlymphoid cells, including the respiratory epithelium. However, it is not known if ciliated bronchial epithelial cells express the HLA-DR genes, if the expression of class II molecules on their surface can be modulated by immune mediators and, finally, if these...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/3.5.431

    authors: Rossi GA,Sacco O,Balbi B,Oddera S,Mattioni T,Corte G,Ravazzoni C,Allegra L

    更新日期:1990-11-01 00:00:00

  • Macrolides inhibit epithelial cell-mediated neutrophil survival by modulating granulocyte macrophage colony-stimulating factor release.

    abstract::Macrolides have been shown to be effective in treating diffuse panbronchiolitis (DPB), although the precise modes of action remain unclear. At sites of airway inflammation, respiratory epithelium is considered an active participant in regulating neutrophil survival. We therefore examined the effect of erythromycin, cl...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2003-0105OC

    authors: Yamasawa H,Oshikawa K,Ohno S,Sugiyama Y

    更新日期:2004-04-01 00:00:00

  • Cytokine expression by neutrophils and macrophages in vivo: endotoxin induces tumor necrosis factor-alpha, macrophage inflammatory protein-2, interleukin-1 beta, and interleukin-6 but not RANTES or transforming growth factor-beta 1 mRNA expression in acut

    abstract::Using a rat model of acute lung inflammation induced by intratracheal instillation of lipopolysaccharide (LPS), we investigated the kinetics of mRNA expression and the potential cellular sources of tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), interleukin (IL)-1 beta, IL-6, RANTES...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.10.2.8110470

    authors: Xing Z,Jordana M,Kirpalani H,Driscoll KE,Schall TJ,Gauldie J

    更新日期:1994-02-01 00:00:00

  • Effect of neutrophil mediators on epithelial permeability.

    abstract::Inflammatory lung disease is associated with increased epithelial permeability, but it is unclear how inflammatory cells alter epithelial permeability. Neutrophils have azurophilic granules containing elastase, cathepsin G, and defensins which are released at sites of inflammation. Experiments using whole animals and ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.13.6.7576710

    authors: Peterson MW,Walter ME,Nygaard SD

    更新日期:1995-12-01 00:00:00